SummaryPlasma HIV-1 RNA and CD4+T-cell counts after HIV-1 seroconversion are important independent markers that predict the clinical course of HIV-1 infection. The prognostic significance of these parameters during primary HIV-1 infection, however, remains largely unknown. In a cohort of 53 male study subjects (age, 33 ± 7 years), who consecutively presented with primary HIV-1 infection, we analyzed the relationship between early plasma HIV-1 RNA, CD4+and CD8+T-cell counts, &bgr;2-microglobulin, and p24-antigen levels determined in the first 3 months and subsequent plasma HIV-1 RNA levels and CD4+T-cell counts 6 to 12 months after onset of primary symptoms. Peak, nadir, and median HIV-1 RNA levels in the first 30 days were already significantly associated with HIV-1 RNA levels at 6 to 12 months (p= .02,p< .0001, andp= .01, respectively). Similarly, early nadir and median CD4+T-lymphocyte counts in the first 30 days showed a significant relationship with CD4+T-cell counts at 6 to 12 months (p= .009 andp= .0008, respectively). Study subjects with an early decline of CD4+counts to <500 cells/&mgr;l had an eightfold higher risk that CD4+counts were <500 cells/&mgr;l at 1 year. Of all evaluated virologic parameters, only nadir HIV-1 RNA at 76 days predicted CD4+counts at 6 to 12 months (p= .006). Early HIV-1 RNA levels and CD4+counts are already associated with the time course of those parameters 6 to 12 months after onset of symptoms. Nadir viral load was the strongest predictor of HIV-1 RNA levels as well as of CD4+counts at 6 to 12 months. An early decline of CD4+T lymphocytes may be a useful clinical prognostic marker for rapid disease progression.